Small molecule inhibitor E-64 exhibiting the activity against African swine fever virus pS273R.

African swine fever (ASF) is a viral disease in swine that results in high mortality in domestic pigs and causes considerable economic losses. Currently, there is no effective vaccine or drugs available for treatment. Identification of new anti-ASFV drugs is urgently needed. Here, the pS273R protein of the African swine fever virus (ASFV) is a specific SUMO-1-like cysteine protease that plays an important role in its replication process. To inhibit virus replication and improve treatment options, a set of small-molecule compounds, targeted inhibitors against the ASFV pS273R protease, were obtained through molecular screening by homology modeling and molecular docking based on structural information of pS273R. Our results clearly demonstrated that the 14th carbon atom of the cysteinase inhibitor E-64 could form one CS covalent bond with the Cys 232 amino acid of the pS273R protease and seven additional hydrogen bonds to maintain a stable binding state. Simultaneously, cell viability, immunophenotyping, and in vitro enzyme activity inhibition assays were performed to comprehensively evaluate E-64 characteristics. Our findings demonstrated that 4 mmol/L E-64 could effectively inhibit the enzyme activity center of the pS273R protease by preventing pS273R protease from lysing pp62, while promoting the upregulation of immune-related cytokines at the transcription level. Moreover, cell viability results revealed that 4 mmol/L E-64 was not cytotoxic. Taken together, we identified a novel strategy to potentially prevent ASFV infection in pigs by blocking the activity of pS273R protease with a small-molecule inhibitor.

Prevalence of African Swine Fever in China, 2018-2019.

African swine fever (ASF) has spread widely across China since 2018. It represents a significant threat to the pig production industry, as no treatment or vaccine is available for this disease. In this study, the geographical distribution and epidemiological features of ASF from all endemic regions of China were analyzed. We focused on the epidemiological data from 149 ASF cases among domestic pigs and wild boars, confirmed during 2018-2019. We found that, in the 1-year period from August 2018 to July 2019, ASF was reported in most geographical regions of the country, which comprises 31 provinces. The outbreaks were mainly located along the important economic zones and tended to increase southward in general. The southwest region was the most severely affected, with 22% of cases, followed by the Northeast, with 20% of cases. There was no significant difference among other regions. Additionally, the overall mean rate of case-incidence/fatality was 12.5% and 64%, respectively, in this period and varied significantly different months, with a general trend towards a decrease over time. The highest incidence rate (30.4%) occurred in April-May 2019, and the highest fatality rate (81.21%) in October-November 2018, demonstrating the marked seasonality in ASF transmission. Furthermore, anthropogenic effects were a major significant risk factor for the spread of the disease. In summary, this initial epidemiological analysis of ASF provides a global perspective on ASF and facilitates detection of trends and patterns, which will be useful for updating preventive actions at a national level and evaluating their impact on public health.